Study of membrane proteins is an important segment of the long range goal of understanding at the molecular level how cells function. The central effort of this envisaged five year program of research is the design, chemical synthesis, and characterization of an array of broadly applicable, new and unique labels for biological membrane studies, with particular emphasis on membrane proteins. In a continuing collaboration with Drs. O.H. Griffith and P.C. Jost at the University of Oregon, these new labels will be used in on-going biochemical and biophysical studies of the properties of beef heart mitochondrial cytochrome oxidase, shark rectal gland Na ion/K ion-ATPase, sarcoplasmic reticulum Ca2-dependent ATP-ase, high density lipoprotein (HDL), as well as other lipid requiring proteins. Examples of envisaged new labels include several unique turn-on-able amino acid specific membrane protein labels, development of novel free radical based membrane protein photolabels, development of a series of diamagnetic isopolar, isosteric structural analogues of doxyl and proxyl nitroxides to be used to explore questions of steric perturbation inherent with the spin labeling method and to determine equilibrium binding constants at specific protein sites, if any, and the development of new heterobifunctional nitroxides potentially useful for saturation transfer ESR spin label studies.